Device for mapping and ablating renal nerves distributed on the renal artery

ABSTRACT

This invention relates to a device for mapping and ablating the renal nerves distributed on the renal artery, said device comprising a guide catheter, a mapping-ablation catheter, a handle and a connector. The guide catheter has at least one lumen and a distal end with adjustable curvature. The mapping-ablation catheter is housed in one of the lumens of the guide catheter and its distal end has one or more electrodes and one or more detecting devices. The distal end of the mapping-ablation catheter is curved, rotatable, and can be extended out of or retracted into the guide catheter. The handle connects the guide catheter and mapping-ablation catheter, and comprises one or more controlling components for controlling the movement of the guide catheter and mapping-ablation catheter. The connector is designed to supply energy to the electrodes.

This application claims priority to the international applicationPCT/IB2012/054303 filed on Aug. 24, 2012, the international applicationPCT/IB2012/054310 filed on Aug. 24, 2012, U.S. 61/693,019 filed on Aug24, 2012 and Chinese application 201310070820.3 filed Mar. 6, 2013. Thecontents of the preceding applications are hereby incorporated in theirentireties by reference into this application. Throughout thisapplication, various publications are referenced. Disclosures of thesepublications in their entireties are hereby incorporated by referenceinto this application in order to more fully describe the state of theart to which this invention pertains.

FIELD OF THE INVENTION

This invention relates to a catheter device system for mapping andablating renal nerves distributed on renal artery so as to improve theaccuracy, effectiveness and safety of catheter-based renal nerveablation.

BACKGROUND OF THE INVENTION

Hyperactivity of renal sympathetic nerve is a pathophysiologicalmechanism in diseases such as congestive heart failure (CHF),hypertension, diabetes, chronic renal failure, arrhythmia and otherheart disorder. The renal sympathetic denervation method has beenapplied recently to treat these diseases because this therapy method canreduce the hyperactivity of sympathetic nerve. In general, all diseaseswith hyperactivity of sympathetic nerve as one of its pathologicalmechanisms can be treated with the renal sympathetic denervationapproach. The renal sympathetic nerve is believed to be both an effectorand sensor of the sympathetic system, thus the pathophysiological statusof the cardiovascular system and other organs can be regulated via therenal sympathetic nerve.

Possible Clinical Applications of Renal Sympathetic DenervationProcedure

1. Hypertension: Krum et al studied the effects of catheter-based renalsympathetic denervation on blood pressure in patients with hypertension.Two studies have been completed and published: Symplicity HTN-1 (Krum etal., 2009; Sadowski et al., 2011) and Symplicity HTN-2 (Esler et al.,2010). One study is under way: Symplicity HTN-3. Symplicity HTN-1 andSymplicity HTN-2 included 50 and 106 patients, with the follow-upperiods of 12 and 6 months, respectively. No detail has been reportedfor Symplicity HTN-3 to date. All studied subjects in these studies werepatients with drug resistance hypertension, i.e. their systolic pressurewas still ≥160 mmHg after administration of at least three types ofanti-hypertensive drugs including a diuretic, or those patients for whomit is impossible to treat their hypertension with drug therapies due tovarious reasons. In Symplicity HTN-1, in 45 patients who had receivedrenal denervation procedure, their average systolic/diastolic bloodpressure dropped from 177/101 mmHg by −14/−10, −21/−10, −22/−11, −24/−11and −27/17 mmHg at 1, 3, 6, 9 and 12 months respectively after thetreatment. The blood pressure level in 5 patients who did not receivethis treatment was increased during the same time period (Krum et al.,2009). In Symplicity HTN-2 study, which was a randomized study having acontrol group, ambulatory blood pressure monitoring replaced manualblood pressure measurement in the outpatient office in order to avoidthe “white coat effect”, and the effects of renal denervation onhypertension further confirmed the results in Symplicity HTN-1. At 1, 3and 6 months after the procedure, systolic and diastolic blood pressurein 52 patients also dropped by 20/−7, −24/−8 and −32/−12 mmHgrespectively from their hypertensive baseline (Esler et al., 2010). Theaverage time spent on the renal denervation procedure was only about 38minutes, low radio frequency energy was used (5˜8 W), the spacingbetween ablation points was at least 5 mm apart, with 4˜6 ablationpoints on each side of renal artery, and the ablation time for eachpoint was 2 min (Sobotka et al., 2012). This method was safe, and up tonow, no side effects such as vascular thrombosis, renal embolism orrenal function impairment were reported.

2. Abnormal glucose metabolism and diabetes: Mahfoud et al studied 37patients with various clinical syndromes of diabetes 3 months after therenal sympathetic denervation procedure. It was found that the fastinglevel of blood glucose dropped from 118 to 108 mg/dL, insulin leveldropped from 20.8 to 9.3 μIU/mL, C-peptide level reduced from 5.3 to 3.0ng/mL, while insulin resistance reduced from 6.0 to 2.4, and the glucoselevel 2 hours after oral glucose tolerance test also reduced by 27mg/dL. In the control group, the blood pressure and the levels of thesemetabolism markers in 13 patients who did not receive renal denervationprocedure were not significant changed (Mahfoud et al., 2011). Theresults demonstrated that renal denervation can improve the insulinresistance and glucose metabolism in patients with diabetes.

3. Sleep apnea syndrome (SAS): Witkowski et al found that renalsympathetic denervation procedure can significantly improve sleep apneain patients with drug resistant hypertension. They found that, 6 monthsafter renal denervation, apnea hypopnea index (AHI) in 10 patients withdrug resistance hypertension accompanied with sleep apnea reduced from16.3 times/h (before the procedure) to 4.5 times/h. These resultsindicate that, in patients with both drug resistant hypertension andsleep apnea, this treatment method can improve the degree of sleep apneawhile reducing the blood pressure of patients (Witkowski et al., 2011).

4. Heart failure: Brandt et al reported that 6 months after renalsympathetic denervation procedure in patients with drug resistancehypertension, the left ventricle hypertrophy index, left ventricularseptum thickness, left ventricular end diastolic volume, isovolumetricrelaxing period and left ventricular filling pressure were significantlyreduced, while the cardiac ejection fraction was increasedsignificantly. Similar changes of these parameters were not observed in18 patients who were served as control group and did not receive thistreatment (Brandt et al., 2012). These results indicate that renalsympathetic denervation procedure can significantly improve cardiacfunctions of patients with cardiac dysfunction. Symplicity-H and REACHare ongoing clinical studies investigating the impacts of renalsympathetic denervation procedure on patients with heart failure, but noresults have yet been published (Sobotka et al., 2012).

5. Chronic kidney diseases and renal failure: hyperactivity andexcessive tone of sympathetic nerve are closely related to theoccurrence and development of chronic renal failure. Factors whichimpair the kidneys can cause hyperactivity of systemic sympathetic nervevia the renal nerve; the pathological high systemic sympathetic tone isharmful to kidney, directly resulting in impairment of renal function(Schlaich et al., 2009). Therefore, reducing the hyperactivity ofsystemic sympathetic nerve by renal sympathetic denervation proceduremay also be a new means to treat chronic kidney diseases and renalfailure. It has been reported that one year after the renal sympatheticdenervation procedure, patients with late stage chronic kidney diseaseand drug resistance hypertension showed no significant change in eGFR(Hering et al., 2012; Hering et al., 2012; Dasgupta et al., 2012). Theresult indicates that the treatment can probably slow down the progressof chronic kidney disease.

6. High sympathetic tone related-cardiovascular diseases: it has beenshown in animal and clinical studies that high sympathetic tone plays animportant role in the occurrence and development of many cardiovasculardiseases (D'Agrosa, 1997; Esler, 1992). Thus, renal sympatheticdenervation which can rebalance the high systemic sympathetic tone bysuppressing the hyperactivity of systemic sympathetic nerve may be usedin treatment of cardiovascular diseases such as arrhythmia and heartfailure.

However, in the existing procedures for renal nerve ablation or otherrenal denervation methods, the distribution of renal nerves is notlocated, and the surgeon does not know on which part of the renal arteryshould the renal denervation procedure be performed. Therefore theoperation is performed blindly, and its treatment effect and safetyshould be further improved and raised. In particular, Brinkmann et alrecently did ablation procedure to remove renal nerves in 12 patientswith hypertension, but blood pressure was only reduced in 3 patientsafter the treatment, and the blood pressure did not reduce in other 7patients after the treatment (Brinkmann et al., 2012). Somehow, theseinvestigators did report changes in blood pressure in the rest of 2patients in their publication. These investigators believed that one ofthe reasons was that the renal nerve ablation procedure was not made atthe distribution point of the renal sympathetic nerve. Brinkmann et al.also expressed that it was not known whether the radio frequency energyapplied in the procedure ablated the renal afferent or efferent nerves.Essentially, surgeons have no clinical indicator to assess and prove ifthe procedure is successfully performed (Brinkmann et al., 2012).Therefore, there is an urgent need clinically for a practical andfeasible method to map the renal sympathetic nerve and the renalparasympathetic nerve, to direct clinical doctors how to remove renalsympathetic nerves in an accurate, effective and safe manner, and toassess and prove if the renal denervation operation is successfullyperformed.

The US patent application, US 2011/0306851 A1, puts forth a specificmethod for renal sympathetic nerve mapping and devices to implementrenal sympathetic nerve mapping for the first time. In the patentspecification, pig experiments were performed to demonstrate how to mapthe distribution of renal sympathetic nerves by applying electricstimulation within renal artery while monitoring changes in artery bloodpressure, heart rate and other physiological parameters. If a givenposition of the renal artery is stimulated and blood pressure and heartrate were increased, that position is determined as a distributed pointby renal sympathetic nerve. This renal sympathetic mapping concept andapproaches were recently confirmed by other investigators. Using dogmodel, Chinushi et al. (Chinushi et al., 2013) reported that onceintra-renal electronic simulation was applied to certain locations ofrenal artery, blood pressure and heart rate were increased. After theselocations were ablated using high radio frequency and the same electricstimulation was applied to the same location again, blood pressure andheart rate no longer changed.

Renal sympathetic denervation provides an alternative therapy to treatdiseases which are related to hyperactivity of sympathetic nerve system,thus there is a clinical need to have devices with functions to performintra-renal artery stimulation and renal denervation. Devices used forthe two above-mentioned studies were not specially designed for renalnerve mapping and ablation. The current catheter and ablation systemswhich have been used by clinicians were designed for cardiac ablationand cardiac diseases such as arrhythmia with very high energy. Theconfiguration and shape of these catheters were not designed accordingto renal artery anatomy and structure but were rather based on coronaryartery/cardiac anatomy and structure. These catheter systems haveelectrodes at their tips which were designed to detect abnormal electricphysiology in cardiac tissues; however, these designs did not meet theneeds of physicians for mapping and ablating renal sympathetic andparasympathetic nerves. An ideal renal nerve mapping and ablationcatheter system should have dual functions: it should deliver electricalstimulations from within the renal artery to map the distributions ofrenal sympathetic and parasympathetic nerves, and also deliver energy toablate renal nerves. At the same time, the shape of the catheter shouldbe optimized for the anatomical structure of renal artery. Using such acatheter system, physicians will be able to deliver intra-renalstimulation, monitor physiological changes in patient during thestimulation, ablate renal sympathetic innervations, and stimulate thesepositions again to evaluate whether a successful renal sympatheticdenervation has been performed. However, up to date, a catheter systemto meet these requirements has not yet been developed.

During renal denervation procedure, the anatomy and structure of therenal artery must be taken into consideration. The variations of therenal artery among individuals are very large such as differences inlength, diameter and bifurcations. Patients with hypertension may haveimplanted renal stents, renal artery stenosis, renal artery plaques orother anatomy abnormalities. If these factors were not taken intoconsideration, for some existing ablation catheter systems with ablationenergy that is too high (renal artery ablation is low energy procedureand it cannot be more than 8 watts), serious side effects may occurduring the procedure such as vessel spasms, edema, renal arteryendothelial denudation, embolism, rupture, necrosis and stenosis. Thus,an ablation catheter system designed according to renal artery anatomy,structure, physiology and biology with low energy, and having bothfunctions of mapping and ablation is an urgent need for renaldenervation.

In summary, current commercially available ablation catheter systems arenot suitable for renal mapping and ablation since they are neitherdesigned based on the anatomy of the renal artery nor for the purpose ofmapping renal sympathetic/parasympathetic nerves. These ablationcatheter systems cannot fulfill the clinical needs of renal denervationwhich require accuracy, efficacy and safety. This invention will addressthese issues.

SUMMARY OF THE INVENTION

This invention provides a catheter device system for mapping andablating renal nerves distributed on renal arteries so as to improve theaccuracy, effectiveness and safety of catheter-based renal nerveablation procedure.

In one embodiment, the present invention provides a device for mappingand ablating the renal nerves distributed on the renal artery,comprising a guide catheter, a mapping-ablation catheter, a handle and aconnector, wherein said guide catheter has at least one lumen and adistal end with adjustable curvature; said mapping-ablation catheter ishoused in one of the lumens of the guide catheter and has a distal endthat comprises one or more electrodes and one or more detecting devices,said distal end of the mapping-ablation catheter is curved and can beextended out of or retracted into the guide catheter and is rotatablealong the central axis of the open end of the guide catheter; saidhandle connects the guide catheter and mapping-ablation catheter andcomprises one or more controlling components, said controllingcomponents are for controlling the movement of the guide catheter andmapping-ablation catheter; and said connector is designed to supplyenergy to the electrode.

In one embodiment, said handle further comprises a fluid-exchangeconduit connected to the guide catheter for controlling fluid enteringor leaving the guide catheter. In another embodiment, said detectingdevices comprise temperature detecting device and resistance detectingdevice. In another embodiment, said electrodes comprise electrodes fordelivering electrical energy, radio frequency energy, laser energy, highintensity focused ultrasound, or for carrying out cryoablation.

In one embodiment, a sealing mechanism is formed between themapping-ablation catheter and guide catheter to control fluid entry orexit.

In one embodiment, the material at the distal end of said guide catheteris the softest, the material at the middle part of the guide catheterhas an intermediate hardness and the material at the proximal end of theguide catheter is the hardest with the hardness of the materialsdistributed in the range 90 A to 80 D in the Shore hardness scale.

In one embodiment, the curvature of the distal end of saidmapping-ablation catheter is maintained by using a traction wire, oneend of the traction wire is fixed to the distal end of themapping-ablation catheter while the other end is fixed to a springinside the handle, wherein when the distal end of the mapping-ablationcatheter is retracted into the guide catheter, the distal end isconfined and stretches the traction wire to compress the spring, whereinwhen the distal end of the mapping-ablation catheter is extended out ofthe guide catheter, its distal end is no longer confined and the springrestores naturally and pulls the traction wire to cause the bending ofthe distal end of the catheter; or by using Ni—Ti shape memory alloywith a preformed shape so that the distal end can maintain the preformedcurvature after assembled into the catheter.

In one embodiment, said controlling components comprise a control knobthat causes the distal end of the guide catheter to bend. In oneembodiment, said controlling components comprise a control knob thatcauses the distal end of the mapping-ablation catheter to extend out ofor withdraw into the guide catheter. In another embodiment, saidcontrolling components comprise a control knob that causes the distalend of the mapping-ablation catheter to rotate. In another embodiment,said controlling components comprise a control knob that causes thedistal end of the mapping-ablation to extend out of or withdraw into theguide catheter, and causes the distal end of the mapping-ablationcatheter to rotate.

The present invention also provides a method of using the devicedisclosed herein for mapping and ablating the renal nerves distributedon a renal artery, said method comprising the following steps: (i)inserting the distal end of the guide catheter of the device into renalartery via the abdominal aorta; (ii) extending the mapping-ablationcatheter out of the guide catheter to establish good contact between theelectrode and the renal artery wall; and (iii) providing energy to theelectrode, so that said energy is delivered to the renal artery wall. Inone embodiment, the curvature of the distal end of the guide catheter isadjustable to make it easier to enter the renal artery. In anotherembodiment, the length of the mapping-ablation catheter extending out ofthe guide catheter is controllable to allow selection of a position toestablish good contact between the electrode and the renal artery wall.In another embodiment, said mapping-ablation catheter can be controlledto rotate around the central axis of the open end of the guide catheterto allow selection of a position to establish good contact between theelectrode and the renal artery wall. In one embodiment, said energy tobe delivered into the renal artery wall comprises energy for nervestimulation and energy for nerve ablation. In another embodiment, saidenergy comprises electric energy, radio frequency energy, laser energy,high density focusing supersonic wave, or for cryoablation. In yetanother embodiment, the above method further comprises the step ofmoving the guide catheter or mapping-ablation catheter, after step(iii), to establish good contact between the electrode and the renalartery wall at a new location.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1-1 shows one embodiment of the catheter device system of thisinvention. The catheter device system comprises a guide catheter (11)having two lumens wherein the curvature of the distal end is adjustable;a steerable mapping-ablation catheter (12) housed within the guidecatheter (11) wherein said mapping-ablation catheter is steerable andhas a distal end with a preformed shape; a handle (13) containingcontrolling components; a fluid-exchange conduit (14) located at the endof the handle that is connected with the guide catheter; a connector(15) at the end of the handle for connecting with the mapping andablating controller; and traction wires connecting the distal end of theguide catheter to the controlling components. The mapping-ablationcatheter is retracted into the guide catheter in the figure shown.

FIG. 1-2 shows the catheter device in FIG. 1-1 when the distal end ofthe guide catheter (11) was bent after the control knob (16) wasrotated.

FIG. 1-3 shows the catheter device in FIG. 1-1 when the mapping-ablationcatheter (12) was extended out of the guide catheter (11) after thecontrol knob (17) was pushed.

FIG. 1-4 shows the catheter device in FIG. 1-1 when the mapping-ablationcatheter (12) extending out of the guide catheter (11) rotated aroundthe central axis of the open end of the guide catheter (11) after thecontrol knob (18) was turned.

FIG. 2-1 shows an embodiment of the distal end (21) of themapping-ablation catheter wherein the tip of the catheter has anelectrode (22) and a temperature detecting device (23), wherein withinthe distal end of the catheter there is a traction wire (21) or shapememory device (25) that cause the distal end to assume a fixed curvatureor adjustable curvature.

FIG. 2-2 shows an embodiment of the distal end of the mapping-ablationcatheter. A sealing mechanism between the tip of the mapping-ablationcatheter (12) and the guide catheter (11) is formed by the smoothsurface of the electrode (22) fitting neatly on the smooth edge of theopen end of the guide catheter (11). The traction wire (24) of themapping-ablation catheter and the traction wire (26) of the guidecatheter (11) are made of stainless steel or Ni—Ti alloy.

FIG. 3-1 shows another embodiment of this invention; said catheterdevice differs from the embodiment of FIG. 1 by having a control knob(19) that can be moved forward and backward or rotated. Themapping-ablation catheter is retracted into the guide catheter in thefigure shown.

FIG. 3-2 shows an embodiment of the mechanism for controlling thebending of the guide catheter (11). The control knob (16) drives thesliding block (31) by means of a screw thread mechanism. Rotating thecontrol knob (16) causes the sliding block (31) move linearly on theslideway (32). One end of a traction wire is fixed to the sliding block(31) while the other end is connected to the tip of the guide catheter.The distal end of the guide catheter will be bent as the traction wireis pulled.

FIG. 3-3 shows an embodiment of the mechanism for extending themapping-ablation catheter (12) out of the guide catheter (11). Thecontrol knob (19) contacts the rotation-fixing block (34) via thestructural component (33) and the rotation-fixing block (34) has agroove ring at its contact with the structural component (33) to ensurethat the structural component will not rotate with the rotation-fixingblock when the rotation-fixing block rotates. When the control knob (19)is pushed, the control knob (19) drives the rotation-fixing block (34)and the mapping-ablation catheter (12) fixed on it to move forward andbackward via the structural component (33) so that the mapping-ablationcatheter (12) can extend out of or withdraw into the guide catheter (11)by moving the control knob (19) forward and backward.

FIG. 3-4 shows an embodiment of the mechanism for rotating themapping-ablation catheter (12) around the central axis of the open endof the guide catheter (11). The control knob (19) contacts therotation-fixing block (34) via the gear set (35). The outside of therotation-fixing block (34) is designed with teeth so that motion thegear set (35) could be transmitted. As the fixing block (36) fixes themapping-ablation catheter (12) on the rotation-fixing block (34) bypressing against the proximal end of the catheter (stainless steel pipe)under the action of a screw, turning the control knob (19) will transmitthe motion to the gear set (35) which then rotates the rotation-fixingblock (34) such that the mapping-ablation catheter (12) will rotatearound the central axis of the open end of the guide catheter (11).

DETAILED DESCRIPTION OF THE INVENTION

The invention will be better understood by reference to the ExperimentalDetails which follow, but those skilled in the art will readilyappreciate that the specific examples are for illustrative purposes onlyand should not limit the scope of the invention which is defined by theclaims which follow thereafter.

In one embodiment, this invention provides a catheter device system formapping and ablating renal nerves distributed on a renal artery, saidcatheter device system comprises a guide catheter having two lumenswherein the curvature of the distal end is adjustable; amapping-ablation catheter housed within the guide catheter wherein saidmapping-ablation catheter is steerable and has a distal end with apreformed shape; a handle containing controlling components; afluid-exchange conduit located at the end of the handle that is linkedto the guide catheter; a connector at the end of the handle forconnecting with external instruments; and traction wires linking thedistal end of the guide catheter to the controlling components.

In one embodiment, this invention provides a single catheter forcarrying out multiple functions that integrates the mapping-ablationcatheter and guide catheter into one device; its electrode can deliverenergy for electrical stimulation or for ablation of underlying nervesin a renal artery so as to achieve the purpose of either mapping orablation of nerves. In another embodiment, this invention allows usersto inject contrast agents, collect blood samples or inject drug fortreatment via the guide catheter. In yet another embodiment, the distalends of the device of this invention is steerable to adjust to thestructure of renal artery or the relative position between the abdominalaorta and the renal artery so that users have better control over thecatheter. This makes it easier for the catheter to enter the renalartery and precisely select the location for which the electrode at thecatheter tip contacts the renal arterial wall. The distal end of thecatheter also has a structure that allows it to anchor at the selectedlocation to ensure that the catheter tip will not be displaced duringthe procedure.

In one embodiment, the controlling components contained in the handlecomprises one or more control knobs for controlling the mapping-ablationcatheter and the distal end of the guide catheter. In anotherembodiment, said control knob is connected to the handle,mapping-ablation catheter and traction wires wherein said connectionwith the handle is fixed or allows rotation or sliding. The connectionwith the mapping-ablation catheter can be fixed connection or coaxialfixed connection.

In one embodiment, one or more traction wires within the guide catheterconnects the tip of said catheter to one or more controlling componentsin the handle so that the distal end of the catheter will bend bymanipulating said one or more controlling components. In anotherembodiment, said controlling components comprise one or more slidingblocks and control knobs wherein said control knob drives the movementof said one or more sliding blocks with a screw thread mechanism.Rotating said control knob causes the sliding block to move linearly ona slideway and, since one end of the traction wire is fixed on thesliding block, and the other end is connected to the tip of the guidecatheter, the distal end of the guide catheter will be bent under thepulling of the traction wire.

In one embodiment, the mapping-ablation catheter is fixed to one or morecontrolling components inside the handle so that said mapping-ablationcatheter can be pushed out of the guide catheter by manipulating saidone or more controlling components. The length that is pushed out canalso be controlled. In another embodiment, said controlling componentscomprise a control knob, a structural part and a rotation-fixing block.In another embodiment, said control knob contacts the rotation-fixingblock via the structural part and the rotation-fixing block has a ringgroove at its point of contact with the structural part to ensure thatthe structural part will not rotate with the rotation-fixing block whenthe rotation-fixing block rotates. In yet another embodiment, when thecontrol knob is pushed, the knob drives the rotation-fixing block tomove forward and backward via the structural part and, since theelectrode at the catheter tip is fixed to the rotation-fixing block,said electrode will move according to the movement of therotation-fixing block. In one embodiment, calibrated markings at thecontrol knob on the handle allow precise control of the length of themapping-ablation catheter that is extended out of or retract into theguide catheter, e.g. 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40mm, 45 mm, 50 mm, 55 mm, 60 mm, 65 mm, 70 mm, 75 mm and 80 mm, etc.Precise control of the length extended out of the guide catheter canensure a minimum spacing between ablation points, such as 5 mm. In oneembodiment, the mapping-ablation catheter extending out of the guidecatheter can be retracted into the guide catheter with the same controlknob or other control knobs.

In one embodiment, the mapping-ablation catheter is fixed to one or morecontrolling components on the handle, so that the mapping-ablationcatheter is rotatable by manipulating one or more controllingcomponents. In another embodiment, said controlling components comprisea control knob, gears or gear set, a rotation-fixing block and a fixingblock. In yet another embodiment, said control knob contacts therotation-fixing block via the gears or gear set and the outside of therotation-fixing block is designed with teeth so that motion from thegears or gear set can be transmitted. In one embodiment, the electrodeat the catheter tip is fixed with the rotation-fixing block so that saidelectrode will move according to the movement of the rotation-fixingblock. In another embodiment, the electrode at the catheter tip is fixedby pressing the fixing block against the proximal end of the catheter(stainless steel pipe) under the action of a screw. In one embodiment,rotation of the control knob drives the gears or gear set which rotatesthe rotation-fixing block, and, in turn, causes the rotation of theelectrode at the catheter tip. In another embodiment, calibratedmarkings at the control knob on the handle allow precise control of theamount by which the mapping-ablation catheter rotates, each markingrepresents rotation by a given angle up to 360° to ensure there is noblind spot when electrical stimulation is delivered. For example, eachmarking represents rotation of the mapping-ablation catheter by 15°.

In one embodiment, the movements of the control knobs occur alongsideways (slide) at the point of contact with the handle. In anotherembodiment, the length of said slideway limits the range of forward orbackward movement of the control knob which in turn preventsoverstretching or breaking of the traction wire. In yet anotherembodiment, for the control knob that rotates around the handle, thereis a small protrusion on the handle that will hook with a smallprotrusion on the control knob. The control knob is free to rotate alongthe slideway within the range when the two protrusions does not meet butover-rotation of the control knob is prevented when the two protrusionshook up, thereby avoiding overstretching or breaking of the tractionwire.

In one embodiment, the mapping-ablation catheter is rotatable in atleast two modes. In one embodiment, the mapping-ablation catheter isrotatable after extending out of the guide catheter. In anotherembodiment, the mapping-ablation catheter is rotatable after fullyretract into the guide catheter.

In one embodiment, the curvature of the steerable distal ends of themapping-ablation catheter and guide catheter can be altered to adjust tothe structure of the renal artery or the relative positions of abdominalaorta and renal artery so that the catheter can be more easily insertedinto the renal artery and operated inside the renal artery.

In one embodiment, the curvature of the distal end of the guide cathetercan be controlled with the control knob on the handle via the tractionwire to ensure that the distal end of the guide catheter can enter therenal artery at a suitable angle.

In one embodiment, the distal end of the mapping-ablation catheter canform a certain curvature. In another embodiment, said curvature canensure that the distal end of the catheter can maintain a givensupportive force within the renal artery and also ensure that the distalend of the catheter can be anchored at a fixed position in the renalartery so that good contact between the distal end of catheter with theinner wall of the artery could be established and the ablation positionis exactly the mapped position. In another embodiment, good contactbetween electrode and inner wall of the artery ensures that theelectrical energy in electrical stimulations can be effectivelydelivered to the artery wall. In yet another embodiment, the energy inradio frequency ablations can be effectively delivered to the arterywall to ablate the nerve.

In one embodiment, to maintain the curvature of the distal end of themapping-ablation catheter, Ni—Ti shape memory alloy material preformedto the desired shape is used so that the distal end can maintain thepreformed curvature after assembled into the catheter. In anotherembodiment, the curvature is achieved by using traction wires, whereinone end of the traction wire is fixed to the distal end of themapping-ablation catheter, and the other end is fixed to a stainlesssteel or Ni—Ti spring inside the handle. In one embodiment, when themapping-ablation catheter is retracted within the guide catheter, thedistal end is confined and stretches the traction wire while at the sametime the spring is compressed. When the distal end of themapping-ablation catheter is extended out of the guide catheter, itsdistal end is no longer confined and the spring restores naturally andpulls the traction wire to cause the bending of the distal end of thecatheter.

In one embodiment, there is one or more electrodes at the tip of themapping-ablation catheter. In one embodiment, said electrodes candeliver electrical energy for nerve mapping. In yet another embodiment,said electrodes can deliver radio frequency ablation energy for renalnerve ablation. In further embodiments, said electrodes can also releaseother types of energy for ablation, such as laser, or high intensityfocused ultrasound, or used in other ablation techniques such ascryoablation, to deliver energy to renal arterial wall to remove renalsympathetic nerve or any other nerve.

In one embodiment, the tip of the mapping-ablation catheter provides oneor more detecting devices. In one embodiment, said device is atemperature detecting device for users to measure the temperature in theartery or on the artery wall. In yet another embodiment, said device isa resistance detecting device for users to measure the resistancebetween the electrode and the artery wall to ensure good contact betweenthe catheter tip and the artery wall.

In one embodiment, the catheter of this invention further provides asealing mechanism to control fluid from entering or leaving the tip ofthe guide catheter. In one embodiment, said sealing mechanism is formedby the smooth surface of the electrode at the tip of mapping-ablationcatheter fitting neatly on the smooth edge of the open end of the guidecatheter. When the mapping-ablation catheter is retracted into the guidecatheter, the close contact between the electrode mapping-ablationcatheter and the edge of the open end of the guide catheter will preventfluid from entering or leaving the open end of the guide catheter. Whenthe sealing mechanism is opened, fluid can enter or leave the guidecatheter as required by the user. In one embodiment, said fluidcomprises contrast agents, blood or drugs. In one embodiment, thecontrol of fluid to enter or leave the guide catheter is for injectingcontrast agent for angiography, collecting blood sample from the renalartery or aorta, or injecting drugs into the renal artery or mainartery.

In one embodiment, the end of the handle has a fluid-exchange conduitconnected to the guide catheter wherein fluid can be led into the distalend of the guide catheter via said fluid-exchange conduit. In anotherembodiment, the distal end of the guide catheter further has one or morelateral holes for fluid to enter or leave the distal end of the guidecatheter.

In one embodiment, the end of the handle has a connector for connectingto external instruments. In one embodiment, said external instrument isa controller for mapping and ablation wherein said controller providesthe electrode of the mapping and ablating catheter with energy forstimulation or ablation of nerves.

In one embodiment, the choice of materials for the guide catheterdepends on the hardness of the material which is selected based on theactual need required when placing the guide catheter into the renalartery. In one embodiment, said guide catheter is made of one or morepolymeric materials of different hardness, wherein said materialscomprises polyether block amide, polyimide or thermoplasticpolyurethane. In one embodiment, said materials are distributed alongdifferent parts of the guide catheter based on their hardness: thematerial at the distal end is the softest, the materials in the middlepart has an intermediate hardness and the material at the proximal endis the hardest. In another embodiment, the hardness of the materials isdistributed in the range 90 A to 80 D in the Shore hardness scale. In afurther embodiment, the different materials can be joined togetherdirectly by butt welding. The guide catheter has at least one big lumenand at least a small lumen. In one embodiment, said big lumen is forhousing the mapping-ablation catheter. In another embodiment, the outerdiameter of the guide catheter is from 1.0 to 5.00 mm, and the innerdiameter is from 0.5 to 4.0 mm. In a further embodiment, said smallcavity is designed to house the traction wire.

In one embodiment, the mapping-ablation catheter comprises a distal endand a proximal end, wherein said distal end and proximal end are madefrom pipes of woven reinforced polymeric material, said polymericmaterials comprises polyether block amide, polyimide or thermoplasticpolyurethane. In another embodiment, said proximal end is made frompipes of metallic materials, wherein said metallic materials comprisesstainless steel or Ni—Ti alloy. In a further embodiment, the outerdiameter of the mapping-ablation catheter is from 0.1 to 3.0 mm.

In one embodiment, the electrode at the tip of the mapping-ablationcatheter is made of metallic materials, wherein said metallic materialscomprises platinum, platinum-iridium alloy, gold or silver. In anotherembodiment, said electrode is circular, elliptical, spiral, spherical,cylindrical or annular in shape. In a further embodiment, the size ofsaid electrode is suitable for use within the renal artery, andcomprises a diameter of 0.1-4 mm or a length of 0.1-4 mm.

In one embodiment, the handle is made of polymeric materials comprisingpolyoxymethylene, acrylonitrile butadiene styrene, polycarbonate,polyamide or polymethylmethacrylate.

In one embodiment, the traction wire is made of materials such asstainless steel or Ni—Ti alloy.

In one embodiment, the catheters of this invention can be in differentmodes during mapping or ablation based on the actual need duringoperation. In one embodiment, the mapping-ablation catheter is fullyretracted into the guide catheter when its tip is placed into the lumenof renal artery for mapping and ablation.

In one embodiment, the device of this invention is used in conjunctionwith all types of medical devices that is compatible with it, whereinsaid medical devices comprise catheter guide wire, traction guide wire,catheter sheath, dilator, or intervention devices for cardiovascular andrenal vascular diseases. In one embodiment, said catheter guide wire canbe placed into the blood vessel of a patient in advance so as to guidethe distal end of the guide catheter to a desired position. In yetanother embodiment, said traction guide wire aids in placing the distalend of the catheter to a suitable position.

This invention further provides a method of using the present catheterdevice for mapping the distribution of renal nerves so that the renalnerve distribution on the renal artery will be mapped and the ablationpoints in the renal artery can be identified in order to optimize therenal nerve ablation procedure. In one embodiment, the method comprisesthe following steps: placing the distal end of the catheter comprisingthe mapping-ablation catheter and the guide catheter into the renalartery lumen; manipulating the control knobs on the handle to move thedistal end of the mapping-ablation catheter or guide catheter so thatthe electrode of the mapping-ablation catheter establishes good contactwith the renal artery wall; delivering electrical stimulation to therenal artery via said electrode while monitoring one or morephysiological parameters for any changes; analyzing the renal nervemapping data comprising said physiological changes to provideinformation about renal nerve distribution and to effectively guideclinical physicians in the renal denervation procedure. In oneembodiment, said physiological parameters comprise blood pressure, heartrate, heart rate variability, muscle sympathetic nerve activity or renalnorepinephrine overflow level. In another embodiment, when electricalstimulation at a position results in changes in said physiologicalparameters, there is distribution of sympathetic nerve, and thestimulated position is suitable for ablation. In yet another embodiment,when the electrical stimulation at a position results in negativechanges in said physiological parameters, there is distribution ofparasympathetic nerve, and ablation should be avoided at the stimulatedposition.

In one embodiment, analysis of the renal nerve mapping data comprisingthe changes in the physiological parameters provide information aboutrenal nerve distribution which can effectively guide clinical physiciansin the renal denervation procedure.

This invention further provides method for mapping and ablating renalnerves with the devices described above and comprises the steps of:

-   (1) Placing the distal end of the device into the abdominal aorta    via a puncture on femoral artery;-   (2) Bend the distal end of the device to adjust to the structure of    the renal artery and the relative position between the renal artery    and abdominal aorta for easier entry into the renal artery;-   (3) Extending the mapping-ablation catheter out of the guide    catheter, and establish good contact between the electrode at the    tip of the mapping-ablation catheter and the renal arterial wall;-   (4) Delivering electrical energy to the position in contact with the    electrode to stimulate any underlying nerves while the physiological    response in heart rate, blood pressure and/or ECG are monitored    concurrently. A stimulated position will be considered as a suitable    location for ablation with underlying sympathetic nerve if the blood    pressure, heart rate and/or heart rate variability derived from ECG    are increased. Ablation should be avoided at a stimulated position    considered to have underlying parasympathetic nerve if the blood    pressure, heart rate and/or heart rate variability derived from ECG    are decreased, or the heart rate alone decreases;-   (5) Applying radio frequency energy to the identified ablation    position via the electrode at the tip of the mapping-ablation    catheter to ablate the nerve while the tip of the mapping-ablation    catheter remains stationary;-   (6) Monitoring the physiological response in heart rate, blood    pressure and/or ECG during ablation; both blood pressure and heart    rate will rise if the radio frequency energy has been successfully    delivered to the sympathetic nerve.-   (7) Delivering electrical energy again to the position in contact    with the electrode to stimulate the underlying nerve after the    ablation; the underlying nerve has been successfully ablated if both    blood pressure and heart rate remain unchanged.-   (8) Rotating the mapping-ablation catheter to bring the electrode at    its tip to another position on the renal artery wall; and-   (9) Repeating steps (1)-(8) at the new contact position if    necessary.

Further details on the nerve mapping procedure are disclosed in thepublished international applications PCT/IB2012/054303 filed on Aug. 24,2012 and PCT/IB2012/054310 filed on Aug. 24, 2012.

EXAMPLE 1

FIGS. 1-1 to 1-4 show one of the embodiments of this invention. As shownin FIG. 1-1, the catheter comprises a steerable guide catheter (11)having lumens, a steerable mapping-ablation catheter (12) having adistal end with preformed shape housed inside the guide catheter, ahandle (13) which contains the controlling components, a fluid-exchangeconduit (14) connected to the guide catheter at the end of the handle, aconnector (15) at the end of the handle for connecting to the mappingand ablating controller, and the traction wires that connect the tip ofthe guide catheter to the controlling components.

In one embodiment, the handle (13) and the controlling componentscontained within are made of polyoxymethylene, acrylonitrile butadienestyrene, or polymethylmethacrylate.

In one embodiment, the guide catheter (11) has an outer diameter of 2.66mm, there is a small lumen of diameter 0.4 mm for the traction wire topass through and a large lumen of 1.57 mm in diameter for themapping-ablation catheter to pass through. The guide catheter (11) ismade of 3 kinds of thermoplastic polyurethane each having differenthardness; the distal end is the softest, the middle part has anintermediate hardness and the proximal end is hardest. In oneembodiment, the hardness for these three parts are respectively 90 A to40 D, 40 D to 70 D, and 70 D to 80 D on the Shore hardness scale. In oneembodiment, the three types of materials are directly butt weldedtogether.

In one embodiment, the mapping-ablation catheter (12) has an outerdiameter of 1.1 mm; its distal end is made of woven polyimide, and itsproximal end is made of stainless steel.

FIG. 2-1 shows the distal end of the mapping-ablation catheter in thesame embodiment shown in FIG. 1-1. The curvature of the distal end ofthe mapping-ablation catheter is maintained by traction wires (24),wherein one end of the traction wire (24) is fixed to the distal end ofmapping-ablation catheter (12), and the other end is fixed to astainless steel or Ni—Ti alloy inside the handle (13). When themapping-ablation catheter is retracted into the guide catheter, thedistal end is confined and stretches the traction wire (24), while atthe same time the spring is compressed. When the distal end of themapping-ablation catheter (12) is extended out of the guide catheter(11), its distal end is no longer confined and the compressed springrestores naturally and pulls the traction wire (24) which causes bendingof the distal end of the catheter. In one embodiment, themapping-ablation catheter is provided with an electrode (22) and atemperature detecting device and resistance detecting device (23).

In one embodiment, the electrode (22) is a round electrode made fromplatinum-iridium alloy, having a diameter of 2.33 mm. The electrode candeliver both electrical and radio frequency energy.

FIG. 2-2 shows the sealing mechanism at the distal end of the sameembodiment shown in FIG. 1-1. In one embodiment, the sealing mechanismbetween the tip of the mapping-ablation catheter (12) and guide catheter(11) is formed by the smooth surface of the round electrode (22) fittingneatly on the smooth edge of the open end of the guide catheter (11).The traction wire (24) of the mapping-ablation catheter and the tractionwire (26) of the guide catheter are made of stainless steel or Ni—Tialloy.

In one embodiment, the controlling components in the handle (13)comprise three control knobs (16, 17, 18), a sliding block (31), astructural component (33), a rotation-fixing block (34), gears or gearset (35) and a fixing block (36).

In one embodiment, the first control knob (16) drives the sliding block(31) with a screw thread mechanism, rotating the first control knob (16)makes the sliding block (31) moves linearly on the slideway (32). Oneend of a traction wire is fixed to the sliding block (31) while theother end is connected to the tip of the guide catheter (12). The distalend of the guide catheter (11) will be bent as the traction wire ispulled.

In one embodiment, the second control knob (17) contacts therotation-fixing block (34) via the structural component (33), therotation-fixing block (34) has a groove ring at the point of contactwith the structural component (33) which ensure that the structuralcomponent will not rotate with the rotation-fixing block when therotation-fixing block rotates. When the second control knob (17) ispushed, the control knob (17) drives the rotation-fixing block (34) tomove forward and backward via the structural component (33). Theelectrode (22) at the tip of the catheter is fixed with respect to therotation-fixing block (34) such that the electrode will move accordingto the movement of the rotation-fixing block. As a result, when thesecond control knob (17) is moved forward or backward, themapping-ablation catheter (12) will extend out of or withdraw into theguide catheter (11). In one embodiment, calibrated markings on thesecond control knob (17) allow precise control of the length of themapping-ablation catheter that is extended out of or retracted into theguide catheter so that the spacing between ablation points is, forexample, at least 5 mm.

In one embodiment, the third control knob (18) contacts with therotation-fixing block (34) via a gear set (35), the outside of therotation-fixing block (34) is designed with teeth so that motion fromthe gears or gear set (35) could be transmitted. The mapping-ablationcatheter (12) is fixed with respect to the rotation-fixing block (34)such that it moves according to the movement of the rotation fixingblock (34). The fixing block (36) fixes the mapping-ablation catheter(12) by pressing against the proximal end of the catheter (e.g.stainless steel pipe) under the action of a screw. Rotating the thirdcontrol knob (18) will transmit this motion to the gears or gear set(35) which then rotates the rotation-fixing block (34) such that themapping-ablation catheter (12) will rotate around the central axis ofthe open end of the guide catheter (11). In one embodiment, calibratedmarkings on the third control knob (18) ensure the mapping-ablationcatheter can be precisely controlled to rotate by, for example, 15° eachtime.

The mapping-ablation catheter (12) in one embodiment can rotate undertwo modes. In the first mode, the distal end of the mapping-ablationcatheter (12) is extended out of the guide catheter (11) when it isrotated; while, in the second mode, the distal end of themapping-ablation catheter (12) is fully retracted into the guidecatheter (11) when it is rotated.

EXAMPLE 2

In this example, the second control knob (17) and the third control knob(18) are the same control knob (19) (FIG. 3-1), that is, the samecontrol knob (19) can control the mapping-ablation catheter to extend orwithdraw and rotate; however, an interlock device ensures that rotationis not possible when this control knob is pushed or pulled. On the otherhand, it is not possible to extend or withdraw the mapping-ablationcatheter when this control knob is rotating. In one embodiment, moving asingle control knob forward and backward can make the mapping-ablationcatheter (12) extend out of or withdraw into the guide catheter (11)(FIG. 3-3); rotating the same single control knob (19) can make themapping-ablation catheter (12) rotate around the central axis of theopen end of the guide catheter (11) (FIG. 3-4).

FIGS. 3-2 to 3-4 show the internal structure of the embodiment inexample 2. The controlling components in the handle (13) comprise twocontrol knobs (16, 19), a sliding block (31), a structural component(33), a rotation-fixing block (34), gears or gear set (35) and a fixingblock (36).

In one embodiment, the first control knob (16) drives the sliding block(31) with a screw thread mechanism, rotating the first control knob (16)causes the sliding block (31) to move linearly on the slideway (32).Since one end of the traction wire is fixed to the sliding block (31)while the other end is connected to the tip of the guide catheter (12),the guide catheter (11) will be bent as the traction wire is pulled(FIG. 3-1).

In one embodiment, the second control knob (19) contacts therotation-fixing block (34) via the structural component (33) and therotation-fixing block (34) has a groove ring at the point of contactwith the structural component (33) to ensure that the structuralcomponent will not rotate with the rotation fixing block when therotation-fixing block rotates. When the second control knob (19) ispushed, the control knob (19) drives the rotation-fixing block (34) tomove forward and backward via the structural component (33). Theelectrode (22) at the tip of the catheter is fixed with therotation-fixing block (34) such that the electrode will move accordingto the movement of the rotation-fixing block. As a result, when thesecond control knob (19) is moved forward and backward, themapping-ablation catheter (12) will extent out of or withdraw into theguide catheter (11). In one embodiment, calibrated markings on thesecond control knob (19) allow precise control of length of themapping-ablation catheter that is extended out of or retracted into theguide catheter so that the spacing between ablation points can be madeat intervals of at least, for example, 5 mm.

In one embodiment, the second control knob (19) contacts with therotation-fixing block (34) via a gear set (35), the outside of therotation-fixing block (34) is designed with teeth so that motion fromthe gears or gear set (35) could be transmitted. The mapping-ablation(12) is fixed with respect to the rotation-fixing block (34) such thatit moves according to the movement of the rotation-fixing block (34).The fixing block (36) fixes the mapping-ablation catheter (12) bypressing against the proximal end of the catheter (e.g. stainless steelpipe) under the action of a screw. Rotating the second control knob (19)will transmit this motion to the gears or gear set (35) which thenrotates the rotation-fixing block such that the mapping-ablationcatheter (12) will rotate around the central axis of the open end of theguide catheter (11). In one embodiment, calibrated markings on thesecond control knob (19) ensure that rotations of the mapping-ablationcatheter can be precisely made by, for example, 15° each time. Thisexample is identical to the first example in all other aspects.

EXAMPLE 3

In this example, the curvature of the distal end of mapping-ablationcatheter is maintained by using shape memory Ni—Ti alloy material with apreformed shape (25) so that the distal end can maintain the preformedcurvature after assembled into the catheter. This example is identicalto the first example in all other aspects.

EXAMPLE 4

In this example, the guide catheter (11) is made of three kinds ofthermoplastic polyurethane of different hardness; the distal end is thesoftest, the middle part has an intermediate hardness while the proximalend is the hardest. In one embodiment, the hardness for these threeparts are respectively 90 A to 40 D, 40 D to 70 D, and 70 D to 80 D onthe Shore hardness scale. In one embodiment, the three types ofmaterials are directly butt welded together. This example is identicalto the first example in all other aspects.

EXAMPLE 5

In this example, the detecting device at the head of themapping-ablation catheter (12) is a resistance detecting device. Thisexample is identical to the first example in all other aspects.

EXAMPLE 6

In this example, there is both a resistance detecting device and atemperature detecting device (23) at the tip of the mapping-ablationcatheter (12). This example is identical to the first example in allother aspects.

EXAMPLE 7

In one embodiment, when any of the devices described above is used, theconnector (15) is connected with an external mapping and ablatingcontroller to provide the electrode at the head of mapping-ablationcatheter with the electrical energy required to stimulate nerves and theradio frequency energy required to ablate nerves.

In one embodiment, a method for mapping and ablating renal nerved withany of the devices described above comprises:

-   (1) Placing the distal end of the catheter into the abdominal aorta    via a puncture on femoral artery;-   (2) Bend the distal end of the device by rotating the first control    knob (16) to adjust to the structure of the renal artery and the    relative position between the renal artery and abdominal aorta for    easier enter the renal artery;-   (3) Extending the mapping-ablation catheter (12) out of the guide    catheter (11) by pushing the second control knob (17 or 19), and    establish good contact between the electrode (22) at the tip of the    mapping-ablation catheter and the renal arterial wall;-   (4) Delivering electrical energy to the position in contact with the    electrode (22) to stimulate any underlying nerves while the    physiological response in heart rate, blood pressure and/or ECG are    monitored concurrently. A stimulated position will be considered a    suitable location for ablation with underlying sympathetic nerve if    the blood pressure, heart rate and/or heart rate variability derived    from ECG are increased. Ablation should be avoided at a stimulated    position considered to have underlying parasympathetic nerve if the    blood pressure, heart rate and/or heart rate variability derived    from ECG are decreased, or the heart rate alone decreases;-   (5) Applying radio frequency energy to the identified ablation    position via the electrode (22) at the tip of the mapping-ablation    catheter to ablate the nerve while the tip of the mapping-ablation    catheter (12) remains stationary;-   (6) Monitoring the physiological response in heart rate, blood    pressure and/or ECG during ablation; both blood pressure and heart    rate will rise if the ratio frequency energy has been successfully    delivered to the sympathetic nerve;-   (7) Delivering electrical energy again to the position in contact    with the electrode (22) to stimulate the underlying nerve after the    ablation. The underlying nerve has been successfully ablated if both    blood pressure and heart rate remain unchanged;-   (8) Rotating the third control knob (18) or the second control knob    (19) to rotate the mapping-ablation catheter (12) to bring the    electrode (22) at its tip to another position on the renal artery    wall, and repeat steps (1)-(8) at the new contact position if    necessary.

REFERENCES

-   1. Brandt M C, Mahfoud F, Reda S et al. Renal sympathetic    denervation reduces left ventricular hypertrophy and improves    cardiac function in patients with resistant hypertension. JACC.    2012, 59: 901-909.-   2. Brinkmann J, Heusser K, Schmidt B M et al. Catheter-Based Renal    Nerve Ablation and Centrally Generated Sympathetic Activity in    Difficult-to-Control Hypertensive Patients: Prospective Case Series.    Hypertension. 2012; 60:1485-1490-   3. Chinushi M, Izumi D, Iijima K et al. Blood Pressure and Autonomic    Responses to Electrical Stimulation of the Renal Arterial Nerves    Before and After Ablation of the Renal Artery. Hypertension.    2013(61):450-456.-   4. D'Agrosa L S. Cardiac arrhythmias of sympathetic origin in the    dog. Am. J. Physiol. Heart Circ. Physiol. 1977, 233(5): H535-H540.-   5. Dasgupta I, Watkin R, Freedman J et al. Renal sympathetic    denervation for resistant hypertension in a patient with severe CKD:    a first report. J. Hum. Hypertens. 2012, 26(10): 639.-   6. Esler M D, Krum H, Sobotka, P A et al. Renal sympathetic    denervation in patients with treatment-resistant hypertension (the    Simplicity HTN-2 Trail): a randomised controlled trial. Lancet.    2010, 376: 1903-1909.-   7. Esler M. The autonomic nervous system and cardiac arrhythmias.    Clin. Auton. Res. 1992, 2(2):133-135.-   8. Hering D, Mahfoud F, Walton A S et al. Renal Denervation in    moderate to severe CKD. JASN. 2012, 23(7): 1250-1257.-   9. Hering D, Walton A S, Krum H, et al. Renal sympathetic nerve    ablation in moderate to severe chronic renal failure: a short term    safety and efficacy pilot study. Hypertension. 2012, 60(2): 502.-   10. Krum H, Schlaich M, Whitbourn R et al. Catheter-based renal    sympathetic denervation for resistant hypertension: a multicentre    safety and proof-of-principle cohort study. Lancet. 2009, 373:    1275-1281.-   11. Mahfoud F, Schlaich M, Kindermann I et al. Effect of renal    sympathetic denervation on glucose metabolism in patients with    resistant hypertension: a pilot study. Circulation. 2011, 123:    1940-1946.-   12. Sadowski J; Bartus K; Kapelak B et al. Catheter-based renal    sympathetic denervation for resistant hypertension: durability of    blood pressure reduction out to 24 months. Hypertension. 2011, 57:    911-917.-   13. Schlaich M P, Socratous F, Hennebry S et al. Sympathetic    activation in chronic renal failure. JASN. 2009, 20(5): 933-939.-   14. Sobotka P A, Krum H, Bohm M et al. The role of renal denervation    in the treatment of heart failure. Curr. Cardiol. Rep. 2012, 14(3):    285-292.-   15. Witkowski A, Prejbisz A, Florczak E et al. Effects of renal    sympathetic denervation on blood pressure, sleep apnea course, and    glycemic control in patients with resistant hypertension and sleep    apnea. Hypertension. 2011, 58: 559-565.

1. A device for mapping and ablating the renal nerves distributed on therenal artery, comprising a guide catheter, a mapping-ablation catheter,a handle and a connector, wherein: said guide catheter has at least onelumen and a distal end with adjustable curvature; said mapping-ablationcatheter is housed in one of the lumens of the guide catheter and has adistal end that comprises one or more electrodes and one or moredetecting devices, said distal end of the mapping-ablation catheter iscurved and can be extended out of or retracted into the guide catheterand is rotatable along the central axis of the open end of the guidecatheter; said handle connects the guide catheter and mapping-ablationcatheter and comprises one or more controlling components, saidcontrolling components are for controlling the movement of the guidecatheter and mapping-ablation catheter; and said connector is designedto supply energy to the electrode.
 2. The device of claim 1, whereinsaid handle further comprises a fluid-exchange conduit connected to theguide catheter for controlling fluid entering or leaving the guidecatheter.
 3. The device of claim 1, wherein said detecting devicescomprise temperature detecting device and resistance detecting device.4. The device of claim 1, wherein a sealing mechanism is formed betweenthe mapping-ablation catheter and guide catheter to control fluid entryor exit.
 5. The device of claim 1, wherein said electrodes compriseelectrodes for delivering electrical energy, radio frequency energy,laser energy, high intensity focused ultrasound, or for carrying outcryoablation.
 6. The device of claim 1, wherein the material at thedistal end of said guide catheter is the softest, the material at themiddle part of the guide catheter has an intermediate hardness and thematerial at the proximal end of the guide catheter is the hardest withthe hardness of the materials distributed in the range 90 A to 80 D inthe Shore hardness scale.
 7. The device of claim 1, wherein thecurvature of the distal end of said mapping-ablation catheter ismaintained: by using a traction wire, one end of the traction wire isfixed to the distal end of the mapping-ablation catheter while the otherend is fixed to a spring inside the handle, wherein when the distal endof the mapping-ablation catheter is retracted into the guide catheter,the distal end is confined and stretches the traction wire to compressthe spring, wherein when the distal end of the mapping-ablation catheteris extended out of the guide catheter, its distal end is no longerconfined and the spring restores naturally and pulls the traction wireto cause the bending of the distal end of the catheter; or by usingNi—Ti shape memory alloy with a preformed shape so that the distal endcan maintain the preformed curvature after assembled into the catheter.8. The device of claim 1, wherein said controlling components comprise acontrol knob that causes the distal end of the guide catheter to bend.9. The device of claim 1, wherein said controlling components comprise acontrol knob that causes the distal end of the mapping-ablation catheterto extend out of or withdraw into the guide catheter.
 10. The device ofclaim 1, wherein said controlling components comprise a control knobthat causes the distal end of the mapping-ablation catheter to rotate.11. The device of claim 1, wherein said controlling components comprisea control knob that causes the distal end of the mapping-ablation toextend out of or withdraw into the guide catheter, and causes the distalend of the mapping-ablation catheter to rotate.
 12. A method of usingthe device of claim 1 for mapping and ablating the renal nervesdistributed on a renal artery, said method comprising the followingsteps: (i) inserting the distal end of the guide catheter of the deviceinto renal artery via the abdominal aorta; (ii) extending themapping-ablation catheter out of the guide catheter to establish goodcontact between the electrode and the renal artery wall; and (iii)providing energy to the electrode, so that said energy is delivered tothe renal artery wall.
 13. The method of claim 12, wherein the curvatureof the distal end of the guide catheter is adjustable to make it easierto enter the renal artery.
 14. The method of claim 12, wherein thelength of the mapping-ablation catheter extending out of the guidecatheter is controllable to allow selection of a position to establishgood contact between the electrode and the renal artery wall.
 15. Themethod of claim 12, wherein said mapping-ablation catheter can becontrolled to rotate around the central axis of the open end of theguide catheter to allow selection of a position to establish goodcontact between the electrode and the renal artery wall.
 16. The methodof claim 12, wherein said energy to be delivered into the renal arterywall comprises energy for nerve stimulation and energy for nerveablation.
 17. The method of claim 16, wherein said energy compriseselectric energy, radio frequency energy, laser energy, high densityfocusing supersonic wave, or for cryoablation.
 18. The method of claim12, further comprising the step of moving the guide catheter ormapping-ablation catheter, after step (iii), to establish good contactbetween the electrode and the renal artery wall at a new location.